EP1221341B1 - Méthode et dispositif pour la détermination du volume d'un échantillon liquide - Google Patents

Méthode et dispositif pour la détermination du volume d'un échantillon liquide Download PDF

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Publication number
EP1221341B1
EP1221341B1 EP01125832A EP01125832A EP1221341B1 EP 1221341 B1 EP1221341 B1 EP 1221341B1 EP 01125832 A EP01125832 A EP 01125832A EP 01125832 A EP01125832 A EP 01125832A EP 1221341 B1 EP1221341 B1 EP 1221341B1
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EP
European Patent Office
Prior art keywords
sample
liquid
ligand
indicator
procedure according
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EP01125832A
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German (de)
English (en)
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EP1221341B8 (fr
EP1221341A1 (fr
Inventor
Werner Hälg
Nikolaus Ingenhoven
Michael Trösch
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Tecan Trading AG
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Tecan Trading AG
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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N35/1009—Characterised by arrangements for controlling the aspiration or dispense of liquids
    • G01N35/1016—Control of the volume dispensed or introduced
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/02—Burettes; Pipettes
    • B01L3/021—Pipettes, i.e. with only one conduit for withdrawing and redistributing liquids
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/02—Burettes; Pipettes
    • B01L3/0241—Drop counters; Drop formers
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01F—MEASURING VOLUME, VOLUME FLOW, MASS FLOW OR LIQUID LEVEL; METERING BY VOLUME
    • G01F25/00—Testing or calibration of apparatus for measuring volume, volume flow or liquid level or for metering by volume
    • G01F25/0092—Testing or calibration of apparatus for measuring volume, volume flow or liquid level or for metering by volume for metering by volume
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N35/1004—Cleaning sample transfer devices
    • G01N2035/1006—Rinsing only the inside of the tip
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N2035/1027—General features of the devices
    • G01N2035/1034—Transferring microquantities of liquid
    • G01N2035/1039—Micropipettes, e.g. microcapillary tubes
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N35/1065—Multiple transfer devices
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00—Chemistry: analytical and immunological testing
    • Y10T436/10—Composition for standardization, calibration, simulation, stabilization, preparation or preservation; processes of use in preparation for chemical testing
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00—Chemistry: analytical and immunological testing
    • Y10T436/10—Composition for standardization, calibration, simulation, stabilization, preparation or preservation; processes of use in preparation for chemical testing
    • Y10T436/101666—Particle count or volume standard or control [e.g., platelet count standards, etc.]

Definitions

  • the invention relates to - according to the preamble of independent claim 1- a method for determining the volume of a sample of a liquid (A), in which - for staining the liquid (A) - a certain concentration of a Chromophoric indicator in this liquid (A) created a sample of the Liquid (A) separated, the optical absorption of the separated sample measured and the volume of the separated sample by correlation of the measured optical absorption with the concentration of the indicator in this liquid (A) is determined.
  • drops with a volume of more than 10 ⁇ l are very simple can be released from the air, because the drops when handled correctly leave the pipette tip with the pipette by itself.
  • the drop size is then by the physical properties of the sample fluid, such as surface tension or viscosity is determined. The drop size thus limits the Dissolution of the amount of liquid to be dispensed.
  • the uptake and delivery i. pipetting liquid samples with a volume of less than 10 ⁇ l on the other hand, it usually requires instruments and techniques which make the delivery of such guarantee small samples.
  • Dispensing a liquid with a pipette tip i. with the tail a device for dispensing / dispensing / dispensing of liquid samples can be done from the air ("from air") or touching a surface.
  • This surface can be the solid surface of a vessel ("on tip touch") be in which the liquid sample is to be delivered. It can also be the Surface of a liquid in this vessel (“on liquid surface”) be.
  • a mixing process following the dispensing is - especially for very small sample volumes in the nano or even picoliter range - too to ensure a uniform distribution of the sample volume in one Diluent is guaranteed.
  • Disposable tips significantly reduce the risk of unwanted transmission of sample parts (contamination).
  • air-Displacement Tips simple disposable tips
  • Their geometry and material for the exact Recording and / or dispensing of very small volumes is optimized.
  • the usage from so-called “positive displacement tips”, which on their inside Having a pump piston is also known.
  • the speed of dispensing determined e.g. largely the way of tearing the drop of the Pipette tip.
  • Single Pipetting aspirates a fluid sample and dispensed elsewhere.
  • Multi Pipetting mode is once aspirated a larger volume of liquid and then in several - mostly equivalent - portions (aliquots) at one or more different Places e.g. into different wells of a standard microtiter plate TM dispensed.
  • the standard DIN 12650 differs essentially in its 4th draft of 1996 Two process categories for testing the accuracy of dispensers. These are gravimetric and non-gravimetric methods. Because not Each laboratory has enough quiet weighing stations and expensive scales the necessary resolution (six decimal places) for performing gravimetric Measurements are made by industry (e.g., EPPENDORF AG, Barkhausenweg 1, D-22339 Hamburg, Germany) photometric tests for Hand pipettes, e.g. offered for the range of sample volumes from 0.2 to 1 ⁇ l.
  • This transmission corresponds to I / I o , ie the ratio of the output intensity and the input intensity of the light rays penetrating the sample.
  • the device for measuring the optical density must also comply with international standards.
  • problems such as the dependence of the measurement on the sample temperature, changes in the test solution and signs of wear in the cuvette must be taken into account.
  • ARTEL Inc. 25 Bradley Drive Westbrook, Maine, USA manufactures this generic system called "Artel PCS TM Pipette Calibration System".
  • the test tube is inserted into the instrument and remains there throughout the calibration procedure.
  • the experimenter opens the lid of the test tube and, with the pipette to be controlled, places a sample corresponding to the desired measuring accuracy into the test tube, whereupon he closes the lid again.
  • the added sample is a solution of "Ponceau S", an organic test substance chosen for its long term stability and good “pipetting” (similar to water, even in high concentrations) and its broad, well-defined absorption peak at 520 nm.
  • the absorption peaks of the copper chloride solution and the test solution "Ponceau S” do not overlap.
  • the test solution also contains biocides to prevent the growth of microorganisms and a pH-stabilizing buffer.
  • the device mixes the two solutions with a built-in mixer and determines the absorbance at 520 nm (Ponceau S) and at 730 nm (copper chloride). On the basis of these two measured values and the known starting concentrations, the volume of the added sample is then calculated.
  • a likewise generic method is known from BE 761 537, which discloses the automatic analysis of various substances with increased accuracy, in particular the automatic analysis, which depends on the sample volume of the substance.
  • chromium in the form of Cr 2 (SO 4 ) 3 .10H 2 O is mixed as an indicator in a sample to obtain therein a certain concentration of chromium (III). Based on the measured chromium (III) concentration, the effective volume of the sample is calculated.
  • the sample volumes are in the milliliter range.
  • the object of the present invention is an alternative method and a corresponding device for determining the volume of a sample suggest a liquid which the shortcomings of the state Technique eliminated and allows a sub-microliter calibration.
  • the metal complex dyes used in accordance with the present invention have extinction coefficients ⁇ of more than 10,000, which, compared to the prior art, allows the use of considerably more sensitive measuring systems:
  • the iron tris-ferrozine complex [Fe (C 20 H 12 N 4 O 6 S 2 ) 3] 4- a ⁇ of about 22,000 (nm at 560)
  • the copper chromazurol S complex [Cu (C 23 H 13 Cl 2 O 9 S] - an ⁇ of about 16,000 (in 522 nm)
  • FIG. 1 An example of a prior art molecule is shown in FIG. 1 and two examples of metal complex dyes proposed for use in the method of the invention for determining the volume of a sample of liquid are shown in FIGS. Showing: Fig. 1 Orange G Fig. 1a structural formula Fig. 1b Top view, room-filling Fig. 1c Side view, room-filling Fig. 2 Copper (I) bis (bathophenanthroline-disulfonklarium) complex Fig. 2a structural formula Fig. 2b View filling the room Fig. 3 Iron (II) tris (ferrozine) complex Fig. 3a structural formula Fig. 3b View filling the room
  • metal complex dyes have (in contrast e.g. to the organic dye Orange G) a three-dimensional, e.g. tetrahedral or octahedral coordination geometry on what is steric As a result, adsorption of such molecules on apolar surfaces is hindered.
  • the ligands may contain ionic groups such as sulfonic or Carboxyl groups are substituted, which is the hydrophilic or the lipophobic Properties further reinforced. Indicator ions in aqueous systems are due their charge and the spherical hydrate shell very hydrophilic and tilt therefore also not for adsorption to apolar surfaces.
  • Adsorption tests with various proposed according to the invention complexes have shown that no significant adsorption on the walls of the Pipetting needles or tubings takes place.
  • the receiving pot In the receiving pot must be an at least stoichiometric amount of chromogenic ligand before or after pipetting the indicator-salt solution available. For sure and quick quantitative reaction can also be a surplus be used on ligands. Possible buffer salts or redox-active Substances that convert the indicator ion into a suitable oxidation state, are also present in the receiving pots. The actual pipetting process However, this is in no way affected, making this measurement system very becomes variable.
  • the indicator ion can be solubilized in any solvent or solvent mixture of appropriate concentration.
  • iron (III) ions can be readily solubilized with 2,4-pentanedione as the [Fe (C 5 H 7 O 2 ) 3 ] complex in nonpolar solvents. From 2,4-pentanedione a wide range of derivatives is available, through which the solubility of the iron complex in any solvent can be adjusted.
  • an auxiliary ligand is either quantitatively displaced by a stronger chromogenic ligand and / or the complexed indicator ion is converted by a redox reaction into an oxidation state that allows the quantitative formation of a stronger complex with the chromogenic ligand. Care must be taken that the absorption spectrum of the auxiliary ligand does not overlap with that of the chromophore complex.
  • ELISA tests Enzyme-Linked Immuno Sorbent Assay
  • PSCHY-REMBEL Clinical Dictionary Walter de Gruyter GmbH & Co. KG, Berlin 1999, 258th Edition
  • ELISA Enzyme-Linked Immuno Sorbent Assay
  • the device acts as an aspirator
  • the device in the first step, acts as an aspirator
  • the device in the second step, the device is used as a dispenser.
  • More recent devices available on the market can dispense several different buffer solutions, used singly or together.
  • Microplate washer must meet - in addition to the known criteria for dispensing - additional specifications in terms of the residual volume (eg, at most 2 ul) after aspiration in a pot.
  • Microplates are preferably made of optically flawless materials. Otherwise Blank value measurements are essential. Particularly preferred Microplates used with flat bottoms and parallel walls. In microplates, especially with 384 or more receiving pots, may be due to surface tension and fluid / wall interaction enhanced meniscus formation occur. When the menisci of liquid pots to liquid pots are irregular, resulting in different path lengths for the photometric measurements, which negatively affect the reproducibility. It is therefore recommended to use microplates with low-binding properties or otherwise modified surfaces to use the increased meniscus formation to suppress.
  • aqueous 0.25 M FeSO 4 solution with FerroZine® and ammonium acetate buffer was used for the calibration curve.
  • the resulting complex solution was stabilized with ascorbic acid.
  • measuring solutions were prepared by dilution corresponding to pipetting volumes of 2.5 nl, 5.0 nl, 10.0 nl, 20.0 nl, 40.0 nl and 80.0 nl in 200 ⁇ l. In each case 12 aliquots of 200 ⁇ l each of these measurement solutions were pipetted by hand into a microplate and the optical absorption or the optical densities (OD) were measured with a microplate photometry reader. By means of the measuring points the calibration curve could be calculated by linear regression.
  • the volume was mixed with demineralized water in the individual receiving wells filled to 200 ul total volume and the Thoroughly mix solutions in the microplates by mechanical shaking.
  • the optical absorption of the colored complex solution in the receiving wells The microplate was then measured in a microplate photometry reader and the volumes are calculated from the calibration curve.
  • volume determinations were in each case 100 .mu.l a 3.25 mM FerroZine® solution buffered with ammonium acetate with ascorbic acid presented in the receiving pot of a microplate. On it were 8 nl, 40 nl, 80 nl and 400 nl of a 0.063 M iron tris (acetylacetonate) solution in pure DMSO pipetted with the automatic pipetting.
  • the volume was made up to 200 ⁇ l total volume with demineralized water in the individual receiving wells and the solutions in the microplates were well mixed by mechanical shaking.
  • the optical absorption of the colored complex solution in the microplate wells was then measured on a microplate photometry reader and the volumes were calculated from the calibration curve.
  • the invention is also applicable to the determination of the volume of a sample of a liquid and a sub-microliter calibration when anions are used as an indicator for staining the liquid (A). Also in such cases, complexation with a specific ligand produces staining of the sample.

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  • General Physics & Mathematics (AREA)
  • Clinical Laboratory Science (AREA)
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  • Investigating Or Analysing Materials By Optical Means (AREA)

Claims (27)

  1. Procédé pour déterminer le volume d'un échantillon d'un liquide (A), dans lequel - pour colorer le liquide (A) - on élabore une concentration définie d'un indicateur chromophore dans ce liquide (A), on sépare un échantillon du liquide (A), on mesure l'absorption optique de l'échantillon séparé et on détermine le volume de l'échantillon séparé par corrélation entre l'absorption optique mesurée et la concentration de l'indicateur dans ce liquide (A), caractérisé en ce que l'on utilise comme indicateur de coloration du liquide (A) des ions qui génèrent la coloration de l'échantillon par complexion avec un ligand spécifique.
  2. Procédé - pour déterminer le volume résiduel d'un échantillon séparé d'un liquide (A) dans un récepteur d'échantillon à partir duquel on a prélevé une partie de l'échantillon de façon telle que seul un reste d'échantillon subsiste encore dans le récepteur d'échantillon - dans lequel - pour colorer le liquide (A) - on élabore une concentration définie d'un indicateur chromophore dans ce liquide (A), on sépare un échantillon du liquide (A) dans le récepteur d'échantillon, on ajoute un diluant au reste d'échantillon et on mesure l'absorption optique du reste d'échantillon dilué, le volume résiduel étant déterminé par corrélation entre l'absorption optique mesurée et la concentration originale de l'indicateur dans ce liquide (A), caractérisé en ce que l'on utilise comme indicateur de coloration du liquide (A) des ions qui génèrent la coloration de l'échantillon par complexion avec un ligand spécifique.
  3. Procédé selon la revendication 1 ou 2, caractérisé en ce que - avant la séparation d'un échantillon - l'indicateur chromophore est complexé avec le ligand et ajouté au liquide (A) en tant que solution de complexe colorée.
  4. Procédé selon l'une des revendications précédentes 1 ou 3, caractérisé en ce que - avant la séparation d'un échantillon - il existe dans un récepteur d'échantillon un volume d'équilibre en tant que partie d'un diluant.
  5. Procédé selon la revendication 1, caractérisé en ce que - avant la séparation d'un échantillon - un sel indicateur est ajouté au liquide (A), un échantillon du liquide (A) est déchargé dans une solution réactionnelle existante avec le ligand chromogène, et complexé alors avec développement de couleur.
  6. Procédé selon la revendication 1, caractérisé en ce que l'indicateur chromophore, avant l'ajout au liquide (A) et pour améliorer sa solubilité dans le liquide (A), est complexé avec un ligand auxiliaire et ajouté au liquide (A), un échantillon du liquide (A) étant déchargé dans une solution réactionnelle existante avec le ligand et alors complexé avec le ligand, par déplacement du ligand auxiliaire et développement de couleur.
  7. Procédé selon la revendication 5 ou 6, caractérisé en ce que le ligand chromogène est ajouté à la solution réactionnelle existante en excès par rapport à la quantité réactionnelle attendue.
  8. Procédé selon l'une des revendications 3 à 7, caractérisé en ce que - après la séparation d'un échantillon dans un récipient récepteur d'échantillon - on ajoute dans ce récepteur d'échantillon un volume de complément.
  9. Procédé selon l'une des revendications précédentes, caractérisé en ce que l'on utilise en tant qu'indicateur des ions métalliques, en particulier Fe++, Fe+++ ou Cu++.
  10. Procédé selon l'une des revendications 1 à 8, caractérisé en ce que l'on utilise en tant qu'indicateur des anions, en particulier F, Cl- ou H2PO4 -.
  11. Procédé selon l'une des revendications précédentes 1 à 8, caractérisé en ce que l'on utilise en tant qu'indicateur des ions métalliques non complexables quantitativement avec le ligand chromogène, en particulier Fe+++.
  12. Procédé selon la revendication 11, caractérisé en ce que les ions métalliques non complexables quantitativement avec le ligand chromogène sont réduits ou oxydés en ions complexables avant la complexion avec le ligand.
  13. Procédé selon la revendication 12, caractérisé en ce que l'on utilise en tant qu'agent réducteur du chlorhydrate d'hydroxylamine, des sels tartrate, de l'acide ascorbique et équivalent, et en tant qu'agent oxydant de l'hexacyanoferrate, du brome élémentaire et équivalent.
  14. Procédé selon une ou plusieurs des revendications précédentes 1 à 9 ou 11 à 13, caractérisé en ce que l'on utilise en tant que ligand un polydentate, comme par exemple FerroZine®, de la bathophénantroline-disodium d'acide disulfonique, de la bathocuproïne-disodium d'acide disulfonique ou Chromazurol S.
  15. Procédé selon une ou plusieurs des revendications précédentes 6 à 9 ou 11 à 14, caractérisé en ce que l'on utilise comme ligand auxiliaire une β-dicétone, par exemple de l'acétonate d'acétyle ou du pentane-2,4-dione-1,5-diol.
  16. Procédé selon la revendication 10, caractérisé en ce que l'on utilise en tant que ligand des systèmes liés de façon covalente en position β et fonctionnalisés à l'anthraquinone, en particulier la Calix[4] pyrrole-anthraquinone.
  17. Système de réalisation du procédé selon une ou plusieurs des revendications 1 à 16, qui comporte un dispositif de distribution et/ou de pipetage, un récepteur d'échantillon pour prélever des échantillons séparés, une solution de test d'un indicateur chromophore avec des ions qui génèrent, par complexion avec un ligand spécifique, la coloration des échantillons, un appareil de mesure de l'absorption optique des échantillons dans le récepteur d'échantillon, et un calculateur destiné à calculer le volume des échantillons séparés.
  18. Système selon la revendication 17, caractérisé en ce qu'il s'agit d'un automate de pipetage et/ou d'un automate de distribution comportant N canaux, N valant en particulier 1, 4, 8, 96 ou 384 canaux.
  19. Système selon la revendication 17, caractérisé en ce qu'il s'agit d'un automate de lavage, en particulier pour plaques de microtitration, comportant N canaux, N valant en particulier 8, 12, 16, 96 ou 384 canaux.
  20. Système selon la revendication 17, 18 ou 19, caractérisé en ce que le récepteur d'échantillon est exécuté en tant que plaque de microtitration ou en tant que matrice de puits.
  21. Système selon la revendication 18 ou 19, caractérisé en ce qu'il comprend une plaque de support présentant les dimensions externes d'une plaque de microtitration et un dispositif de mesure de la température des incubateurs de plaques de microtitration.
  22. Trousse de test permettant de réaliser le procédé selon une ou plusieurs des revendications 1 à 16 et/ou dans un système selon une ou plusieurs des revendications 17 à 21, caractérisé en ce qu'elle comprend au moins une solution de test, définie en concentration et en absorption optique, d'un indicateur chromophore avec des ions qui génèrent, par complexion avec un ligand spécifique, la coloration de l'échantillon.
  23. Trousse de test selon la revendication 22, caractérisée en ce qu'elle comprend de plus une solution réactionnelle définie avec un ligand chromogène.
  24. Trousse de test selon la revendication 22 ou 23, caractérisée en ce qu'elle comprend de plus un agent réducteur ou un agent oxydant.
  25. Trousse de test selon l'une des revendications 22 à 24, caractérisée en ce qu'elle comprend de plus un tampon de diluant et/ou un ligand auxiliaire.
  26. Trousse de test selon l'une des revendications 22 à 25, caractérisée en ce qu'elle comprend de plus des plaques de microtitration.
  27. Trousse de test selon la revendication 26, caractérisée en ce que les plaques de microtitration présentent une géométrie sélectionnée ou une propriété de surface sélectionnée.
EP01125832A 2000-11-17 2001-10-30 Méthode et dispositif pour la détermination du volume d'un échantillon liquide Expired - Lifetime EP1221341B8 (fr)

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CH22522000 2000-11-17
CH22812000 2000-11-23
CH22812000 2000-11-23

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EP1221341A1 EP1221341A1 (fr) 2002-07-10
EP1221341B1 true EP1221341B1 (fr) 2005-11-23
EP1221341B8 EP1221341B8 (fr) 2006-02-01

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US (1) US7247483B2 (fr)
EP (1) EP1221341B8 (fr)
JP (1) JP4127999B2 (fr)
AT (1) ATE310582T1 (fr)
AU (1) AU2001295361A1 (fr)
CA (1) CA2363475A1 (fr)
DE (1) DE50108157D1 (fr)
WO (1) WO2002040161A1 (fr)

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Publication number Priority date Publication date Assignee Title
US6741365B2 (en) * 2001-12-12 2004-05-25 Artel, Inc. Photometric calibration of liquid volumes
DE10212557A1 (de) * 2002-03-14 2003-09-25 Univ Schiller Jena Verfahren zur Charakterisierung hochparallelisierter Liquidhandlingtechnik mittels Mikroplatten sowie Testkit zur Durchführung des Verfahrens
JP4722551B2 (ja) * 2005-05-16 2011-07-13 日本電信電話株式会社 溶液吐出量評価装置及び方法
US8003405B2 (en) * 2005-12-16 2011-08-23 Artel, Inc. Calibrating dispensing device performance for complex and/or non-aqueous liquids
US7772008B2 (en) * 2006-01-06 2010-08-10 Artel, Inc. Method and apparatus for determining liquid volume
DE102006016822B4 (de) * 2006-04-07 2011-12-29 Söll Gmbh Volumenbestimmung von Gewässern
US7998747B2 (en) * 2006-09-15 2011-08-16 Artel, Inc. Quantitative dual-dye photometric method for determining dilution impact
EP2657699B1 (fr) 2007-10-02 2017-03-22 Theranos, Inc. Dispositifs modulaires à utiliser sur place et leurs utilisations
AU2013205052B2 (en) * 2007-10-02 2015-04-16 Labrador Diagnostics Llc Modular point-of-care devices and uses thereof
US7791716B2 (en) * 2008-04-07 2010-09-07 Artel, Inc. System and method for liquid delivery evaluation using solutions with multiple light absorbance spectral features
US8404158B2 (en) 2008-04-07 2013-03-26 Artel, Inc. System and method for liquid delivery evaluation using solutions with multiple light absorbance spectral features
TWI748368B (zh) 2011-01-21 2021-12-01 美商拉布拉多診斷有限責任公司 樣本使用最大化之系統及方法
US9268915B2 (en) 2011-09-25 2016-02-23 Theranos, Inc. Systems and methods for diagnosis or treatment
US8840838B2 (en) 2011-09-25 2014-09-23 Theranos, Inc. Centrifuge configurations
US9664702B2 (en) 2011-09-25 2017-05-30 Theranos, Inc. Fluid handling apparatus and configurations
US20140170735A1 (en) 2011-09-25 2014-06-19 Elizabeth A. Holmes Systems and methods for multi-analysis
US9619627B2 (en) 2011-09-25 2017-04-11 Theranos, Inc. Systems and methods for collecting and transmitting assay results
US9632102B2 (en) 2011-09-25 2017-04-25 Theranos, Inc. Systems and methods for multi-purpose analysis
US8475739B2 (en) 2011-09-25 2013-07-02 Theranos, Inc. Systems and methods for fluid handling
GB2494693B (en) 2011-09-16 2018-01-17 Starna Scient Limited Method for determining the path length of a sample and validating the measurement obtained
US9250229B2 (en) 2011-09-25 2016-02-02 Theranos, Inc. Systems and methods for multi-analysis
US9810704B2 (en) 2013-02-18 2017-11-07 Theranos, Inc. Systems and methods for multi-analysis
US10012664B2 (en) 2011-09-25 2018-07-03 Theranos Ip Company, Llc Systems and methods for fluid and component handling
JP5483134B2 (ja) * 2012-10-09 2014-05-07 独立行政法人産業技術総合研究所 微量液滴の体積測定方法及び装置
US10401373B1 (en) 2013-02-18 2019-09-03 Theranos Ip Company, Llc Systems and methods for analyte testing and laboratory oversight
US11008628B1 (en) 2013-02-18 2021-05-18 Labrador Diagnostics Llc Systems and methods for analyte testing and laboratory oversight
US10422806B1 (en) 2013-07-25 2019-09-24 Theranos Ip Company, Llc Methods for improving assays of biological samples
US11360107B1 (en) 2014-02-25 2022-06-14 Labrador Diagnostics Llc Systems and methods for sample handling
WO2017039690A1 (fr) 2015-09-04 2017-03-09 Qualigen, Inc. Systèmes et procédés pour la vérification d'échantillon
DE102016208967B4 (de) 2016-05-24 2024-04-18 Axagarius Gmbh & Co. Kg Photometer mit quantitativer Volumenerfassung
CN109307541B (zh) * 2018-11-29 2020-03-24 郑州安图生物工程股份有限公司 一种发光板单孔残液的体积测量方法

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4354376A (en) * 1980-03-03 1982-10-19 Medical Laboratory Automation, Inc. Kit for calibrating pipettes
US5061639A (en) * 1989-12-06 1991-10-29 E. I. Dupont De Nemours And Company Liquid dispenser accuracy verification method
US5298978A (en) * 1992-02-28 1994-03-29 Artel, Inc. Pipette calibration system
US5492673A (en) * 1992-02-28 1996-02-20 Artel, Inc. Reagent system for calibration of pipettes and other volumetric measuring devices
US5320969A (en) * 1992-10-22 1994-06-14 Miles Inc. Method, composition and device for the semiquantitative determination of specific gravity of a test sample

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ATE310582T1 (de) 2005-12-15
EP1221341B8 (fr) 2006-02-01
JP2002228587A (ja) 2002-08-14
DE50108157D1 (de) 2005-12-29
CA2363475A1 (fr) 2002-05-17
JP4127999B2 (ja) 2008-07-30
US20020149772A1 (en) 2002-10-17
US7247483B2 (en) 2007-07-24
WO2002040161A1 (fr) 2002-05-23
EP1221341A1 (fr) 2002-07-10
AU2001295361A1 (en) 2002-05-27

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